脓毒症小鼠急性肾损伤时Erbin与Bax/Bcl-xL介导的细胞凋亡的关系  

Relationship between Erbin and Bax/Bcl-xL-mediated cell apoptosis during sepsis-induced acute kidney injury in mice

作　　者：刘喻萍 靖国庆 方清 左静[1] 杨丞 宋学敏[1] Liu Yuping;Jing Guoqing;Fang Qing;Zuo Jing;Yang Cheng;Song Xuemin(Department of Anesthesiology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院麻醉科,武汉430071

出　　处：《中华麻醉学杂志》2022年第12期1516-1519,共4页Chinese Journal of Anesthesiology

摘　　要：目的:评价脓毒症小鼠急性肾损伤时Erbin与Bax/Bcl-xL介导的细胞凋亡的关系。方法:SPF级雄性野生型C57BL/6小鼠32只,SPF级雄性Erbin(-/-)C57BL/6小鼠32只,6~8周龄,体重20~30 g。采用随机数字表法分别将两种小鼠分为2组(n=16):野生型假手术组(WT+Sham组)和野生型脓毒症组(WT+S组)、Erbin(-/-)假手术组(EKO+Sham组)和Erbin(-/-)脓毒症组(EKO+S组)。采用中度盲肠结扎穿孔(CLP)法制备脓毒症模型。记录CLP后7 d生存情况。于CLP后24 h时,检测血清TNF-α、IL-10、IL-1β、Cr、BUN和LDH浓度,随后取肾组织进行肾损伤评分,TUNEL法确定细胞凋亡率,采用Western blot法测定cleaved-caspase-3、Bcl-xL和Bax的表达。结果:与各假手术组比较,各脓毒症组生存率降低,血清IL-1β、IL-10、TNF-α、Cr、BUN和LDH浓度、肾损伤评分和细胞凋亡率升高,肾组织Bax和cleaved-caspase-3表达上调,Bcl-xL表达下调(P<0.05);与WT+S组比较,EKO+S组生存率降低,血清IL-1β、LDH、TNF-α、Cr和BUN浓度和肾损伤评分升高,血清IL-10浓度降低,肾组织细胞凋亡率升高,Bax和cleaved-caspase-3表达上调,Bcl-xL表达下调(P<0.05)。结论:Erbin可抑制Bax/Bcl-xL介导的细胞凋亡,参与脓毒症小鼠急性肾损伤的内源性保护机制。Objective To evaluate the relationship between Erbin and Bax/Bcl-xL-mediated cell apoptosis during sepsis-induced acute kidney injury in mice.Methods Thirty-two SPF male wild type C57BL/6 mice,32 SPF male Erbin(-/-)C57BL/6 mice,aged 6-8 weeks,weighing 20-30 g,were divided into 2 groups(n=16 each)using the random number table method:wild type sham operation group(WT+Sham group),wild type sepsis group(WT+S group),Erbin(-/-)sham operation group(EKO+Sham group),and Erbin(-/-)sepsis group(EKO+S group).The sepsis model was established using the moderate cecal ligation and puncture(CLP)in anesthetized animals.The survival rates within 7 days after CLP were recorded.The serum concentrations of tumor necrosis factor-alpha(TNF-α),interleukin-10(IL-10),IL-1β,creatinine(Cr),blood urea nitrogen(BUN)and lactic dehydrogenase(LDH)were determined at 24 h after CLP.Then the renal tissues were taken for assessment of renal injury which was scored and for determination of the apoptosis rate(by TUNEL)and expression of cleaved-caspase-3,Bcl-xL and Bax(by Western blot).Results Compared with sham operation groups,the survival rates were significantly decreased,the serum concentrations of IL-1β,IL-10,TNF-α,Cr,BUN and LDH,renal injury score and apoptosis rate were increased,the expression of Bax and cleaved-caspase-3 was up-regulated,and the expression of Bcl-xL was down-regulated in sepsis groups(P<0.05).Compared with WT+S group,the survival rates were significantly decreased,the serum concentrations of IL-1β,LDH,TNF-α,Cr and BUN and renal injury score were increased,the serum concentration of IL-10 was decreased,the apoptosis rate of renal tissues was increased,the expression of Bax and cleaved-caspase-3 was up-regulated,and the expression of Bcl-xL was down-regulated in EKO+S group(P<0.05).Conclusions Erbin can inhibit Bax/Bcl-xL-mediated cell apoptosis and is involved in endogenous protective mechanism against sepsis-induced acute kidney injury in mice.

关 键 词：脓毒症 急性肾损伤 细胞凋亡 BCL-2相关X蛋白质 bcl-X蛋白质 ERBIN 

分 类 号：R459.7[医药卫生—急诊医学] R692[医药卫生—治疗学]